Abstract: "Aging" is a topic that everyone must face, but it is also a topic that is secretive, no one wants to admit their aging, and because of this, anti-aging research has become the lifelong pursuit of many biologists. Today, aging research is entering a new era of medical, commercial and social significance. I believe that in the future, the progress of science and technology will help us alleviate the aging process.
In recent years, "age anxiety", "body anxiety" and "appearance anxiety" have become the three mountains that weigh on us, and age anxiety is ranked first. The "women's 30-year-old anxiety" and "workplace 35-year-old anxiety" of the major marketing numbers have invisibly created a tense atmosphere, adding to the age anxiety of the public, making it difficult for us to face the number that is increasing year by year. But one day, we may be able to discover a new secret to fight aging and truly achieve anti-aging!
Scientists turn back the clock
Makes the skin cells 30 years younger
Recently, scientists have discovered the secret to making the skin younger. Researchers from the Babaham Institute at the University of Cambridge have developed a new technique that rejuvenates skin cells, which can make subjects' skin cells about 30 years younger and directly return to youth, the study is titled "Multi-omic rejuvenation of human cells by maturation phase transient reprogramming" (Figure 1), Posted on eLife. This study shows that researchers have developed a complete cell reprogramming technique called "maturity transient reprogramming (MPTR)" that promotes collagen production and restores other aspects of the cell[1]. While the study is still in the early stages of exploration, it could revolutionize regenerative medicine.
Figure 1 Research results (Source: eLife)
Based on stem cell technology, the researchers used cell reprogramming techniques to overcome the problem of completely eliminating cell identity by stopping partial programming throughout the process. This allowed the researchers to find a precise balance between reprogramming cells, allowing cells to return to youthfulness while still being able to restore their characteristic cellular function. The study involved fibroblasts in human skin, which secrete collagen, provide structural support for skin tissue and heal wounds.
In this study, the researchers first transferred the aging fibroblasts to the 4 transcription factors found by Shinya Yamanaka, and after 10-17 days or so, these fibroblasts entered the mature stage, and then these factors were removed to allow the cells to return to a normal state. In the intermediate stage, the morphology and gene expression level of fibroblasts change, and after removal, they return to the fibroblast state again (Figure 2).
Figure 2 Cell change phase (Source: eLife)
To demonstrate that the cells were rejuvenated, the researchers monitored changes in the characteristics of aging. They employed multiple measurements of cell age, the first being an epigenetic clock and the second being a transcriptome, and through these two measurements, the researchers eventually found that the reprogrammed cells matched the characteristics of cells that were 30 years younger. Cell reprogramming techniques not only make cells look younger on the surface, but also function more young.
In addition, it is worth mentioning that this research may also open up other treatment possibilities. The researchers observed that the technique also had an impact on genes associated with diseases that arise as a result of age, such as the APBA2 gene associated with Alzheimer's disease and the MAF gene associated with cataract development both showing a younger trend. As the researchers say, this technique promises to lead to valuable discoveries that will open up an amazing therapeutic field.
Anti-aging research is ongoing
Or can fight against the "pig killing knife" of the years
1
Rapamycin stops cell aging
The Linda Partrige research group of the Max Planck Institute for Aging Biology in Germany, together with researchers at University College London in the United Kingdom and the University of Michigan in the United States, published a report entitled "A TORC1-histone axis regulates chromatin organisation andnon-canonical induction of autophagy to ameliorate ageing." (Figure 3) research paper, this paper reveals a completely new mechanism of the drug rapamycin and mTOR signaling pathways in delaying aging [2].
Figure 3 Research results (Source: elife)
Changes in age-related histone levels can be seen in many species, but it is unclear whether changes in histone expression can be used to improve aging in multicellular organisms. In this study, the researchers screened for the effect of rapamycin on aging-related biomarker signals by drosophila and found that rapamycin was able to specifically increase the expression levels of intestinal histone H3 and H4 in Drosophila by recruiting eIF3 transcription factors. Increased levels of expression of these two histones can prevent age-related decline in intestinal function on the one hand, and rapamycin-induced longevity and intestinal health on the other (Figure 4) [2].
Fig. 4 Rapamycin treatment to improve the expression level of intestinal histone flies intestinal health and longevity (Source: elife)
In summary, this study shows that rapamycin has a health-promoting, anti-aging effect, an important discovery that provides a basis for emerging targeted drug therapies and may become the focus of anti-aging drug research and development.
2
Can antioxidants fight aging?
Oxidative stress is one of the focuses of anti-aging research. An antioxidant protein, nicotinamide adenine dinucleotide (NAD+), is the core of energy metabolism. NAD+ consists of two nucleotides linked by a phosphate group, one containing an adenine nucleoside base and the other containing nicotinamide, a substance essential for repairing damaged DNA and assisting in mitochondrial function. The BUCK Institute researchers working on anti-aging research published in Nature in a study titled "NAD+ metabolism and its roles in cellular processes during ageing" (Figure 5) detail the role of NAD+ in metabolic pathways, DNA repair, cellular immunity, and senescence [3].
Figure 5 Research results (Source: Nature Reviews)
Studies have shown that NAD+ directly and indirectly affects many key cellular functions, including metabolic pathways, DNA repair, chromatin remodeling, cellular senescence, and immune function, which are essential for maintaining tissue and metabolic homeostasis and healthy aging[3]. Its effects are as follows: to improve the metabolic system. The lack of NAD+ can lead to metabolic disorders in the body, which in turn increases the risk of diabetes, cardiovascular disease, stroke, cancer and other diseases. NAD+ activates a variety of coenzymes, promotes metabolism and maintains good health, and enhances cardiovascular function. Increased NAD+ levels prevent negative effects on the heart due to insufficient blood; restore immune function. Supplementation with NAD+ can regulate the activity of proteases such as CD38 and PARPs, resulting in a decrease in pro-inflammatory cytokines, which in turn restore immune function and alleviate neurodegeneration. Increasing NAD+ levels can effectively reduce the accumulation of harmful proteins, enhance information transmission between brain cells, and then restore brain cognitive function; anti-aging prolongs life. Increasing NAD+ levels can promote cell metabolism, enhance mitochondrial function, enhance cell activity, and effectively delay human aging.
3
Inhibition of special molecules is expected to reverse muscle aging
With the increase of age, the structure and function of human skeletal muscle will change, muscle mass will continue to be lost, muscle strength will decline sharply, reducing the quality of life of the elderly at the same time, but also increasing the social medical burden. However, there is no effective anti-muscle aging program. In a study published in Science titled "Inhibition ofprostaglandin-degrading enzyme 15-PGDH rejuvenates aged muscle mass and strength" (Figure 6), researchers from Stanford University in the United States found that reducing the activity of the 15-PGDH protein by one month restored the mass and strength of aging muscles [4].
Figure 6 Research results (Source: Science)
In previous studies, researchers found that prostaglandin E2 (PGE2) activates muscle stem cells and repairs damaged muscles. By examining the prostaglandin composition of skeletal muscle in older mice, the researchers found that their PGE2 levels decreased, and PGE2 was degraded by the prostaglandin enzyme 15-PGDH. The researchers further examined the levels and activity of 15-PGDH in the skeletal muscle of elderly mice and found that its levels and activity were elevated. And, mRNA and protein levels of 15-PGDH in the muscles of older mice also increased significantly compared to younger mice. These all suggest that 15-PGDH is an important driver of the decline in prostaglandin levels in the muscles of elderly mice.
The researchers treated the old mice with a 15-PGDH inhibitor, and after a month of treatment, the researchers found that the activity of 15-PGDH in the muscles of the older mice was reduced and PGE2 levels increased, comparable to that of young muscles. Furthermore, the treated elderly mice experienced increases in muscle fiber cross-sectional area, muscle mass, and muscle strength, and endurance, suggesting that a systematic decrease in 15-PGDH activity was sufficient to inhibit skeletal muscle atrophy and enhance muscular function in older mice[4].
Most promising
Research anti-aging therapies
1
Metformin
Metformin is a widely used anti-diabetic drug, scientists have found that it can target a variety of molecular mechanisms of aging, there have been more and more studies found that metformin can delay aging, prolong healthy life. A study published in Cell Cycle titled "Metformin slows downaging and extends life span of female SHR mice" (Figure 7) found that metformin-treated mice had an average lifespan of approximately 40 percent longer [5].
Figure 7 Research results (Source: Cell Cycle)
In this study, the researchers treated female long-distance SHR mice with metformin, with an average lifespan increase of 37.8% after 20 months compared to the control group, a 20.8% increase in average lifespan in the last 10% of survivors, and a maximum lifespan of 2.8 months (+10.3%) [5]. Therefore, from the above data, metformin can directly and significantly prolong life.
The anti-aging mechanism of metformin is more complex, mainly including two pathways: one is to activate AMPK through metabolic pathways, and the other is to inhibit the electron delivery system of mitochondrial type I complexes through antioxidant pathways. On the one hand, it can inhibit the expression of inflammatory cytokines, such as IL-6 and IL-1β; on the other hand, it can activate UIK1 and promote autophagy function, which in turn can lead to a series of downstream effects: reducing epigenetic changes and stem cell dysfunction, and maintaining protein homeostasis [6].
2
Rapamycin analogues
Rapamycin, also known as sirolimus and its analogue everolimus, is a novel anti-rejection drug of macrolides, the newest potent immunosuppressant in the world, and is clinically used for the anti-rejection response of organ transplants and the treatment of autoimmune diseases. Studies have shown that reducing the dosage of rapamycin and its analogues can reduce its toxic side effects while maintaining a certain anti-aging effect. Relevant experts believe that the current realistic goal is to study whether rapamycin can effectively treat aging-related diseases, such as cancer treatment in the clinical stage. As technology continues to advance, we can optimistically estimate that it is entirely possible to live an additional 10 years in a relatively healthy way in the future.
3
Senolytics
Although few trials have been conducted in humans, Senolytics is one of the most promising anti-aging drugs in animal trials. Senescent cell lysate Senolytics mainly target senescent cells, and their role is to remove these senescent cells. Senescent cells are cells in the human body that have a stagnant cell cycle, they do not continue to divide but they cannot die, and they also secrete a series of pro-inflammatory factors, which may re-engineer the extracellular environment and induce abnormal cell death. Senescent cells are also associated with the pathological occurrence of osteoporosis, atherosclerosis, hepatic steatosis, pulmonary fibrosis, and osteoarthritis. Related studies have shown that in the human body, senescent cells account for up to 15% of the total number of cells in the human body, and if these senescent cells can be eliminated by some means, it may produce great benefits. Senolytics can target the removal of senescent cells, or can effectively reverse the aging of some organs and tissues in the human body.
Although aging is inevitable, scientists have long sought effective ways to slow down the aging process. Moreover, through various studies, scientists have also confirmed that aging can be changed, and by intervening in biological systems, such as cellular aging, the whole body environment and the gut microbiome, the aging phenotype can be fully slowed down, thereby reducing age-related functional decline. I believe that the future "return to youth" may no longer be a fantasy!
Source: Penguin, for academic exchange only.
Written by | Muzijiu
Typography | essay competition
End
Resources:
[1] Gill D, Parry A, Santos F, et al. Multi-omic rejuvenation of human cells by maturation phase transient reprogramming. Elife. 2022 Apr 8;11:e71624. doi:10.7554/eLife.71624. Epub ahead of print. PMID: 35390271.
[2] Lu YX, Regan JC, E er J, et al. ATORC1-histoneaxis regulates chromatin organisation and non-canonical induction of autophagyto ameliorate ageing. Elife. 2021 May 14;10:e62233. doi: 10.7554/eLife.62233.PMID: 33988501; PMCID: PMC8186904.
[3] Covarrubias AJ, Perrone R, Grozio A, et al. NAD+ metabolism andits roles in cellular processes during ageing. Nat Rev Mol Cell Biol. 2021Feb;22(2):119-141. doi: 10.1038/s41580-020-00313-x. Epub 2020 Dec 22. PMID:33353981; PMCID: PMC7963035.
[4] Palla AR, Ravichandran M, Wang YX, et al. Inhibition of prostaglandin-degrading enzyme 15-PGDH rejuvenates aged musclemass and strength. Science. 2021 Jan 29;371(6528):eabc8059. doi:10.1126/science.abc8059. Epub 2020 Dec 10. PMID: 33303683; PMCID: PMC7938328.
[5] Anisimov VN, Berstein LM, Egormin PA, et al. Metformin slows down aging and extends life span of female SHR mice. Cell Cycle. 2008 Sep 1;7(17):2769-73. doi:10.4161/cc.7.17.6625. Epub 2008 Sep 11. PMID: 18728386.
[6]https://www.xiahepublishing.com/2475-7543/MRP-2021-001
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